POS0297 EFFECTIVENESS AND SAFETY OF SECUKINUMAB IN AXIAL SPONDYLOARTHRITIS: A 24-MONTH PROSPECTIVE, MULTICENTER REAL-LIFE STUDY
Authors: G. Cozzi, M. Lorenzin, M. S. Chimenti, S. D’angelo, A. Marchesoni, C. Salvarani, E. Lubrano, L. Costa, Y. Dal Bosco, E. Fracassi, A. Ortolan, M. Ferraioli, A. Carriero, E. Visalli, R. Bixio, F. Desiati, A. Bergamini, E. Pedrollo, A. Doria, R. Foti, A. Carletto, R. Ramonda
Journal: Annals of the Rheumatic Diseases (2022)

Background Axial Spondyloarthritis (axSpA) can be distinguished in radiographic axSpA (r-axSpA) and non-radiographic (nr-axSpA). Secukinumab (SEC) is a novel treatment for axSpA, but data from real-life are still missing. Objectives To evaluate, in a multicentric-Italian-cohort of axSpA patients on SEC followed for 24-months: a)the long-term effectiveness and safety of SEC; b)the drug-retention-rate and low-disease-activity (LDA) measured as BASDAI&lt;4/ASDAS&lt;2.1 and very-low-disease-activity (VLDA) measured as BASDAI&lt;2/ASDAS&lt;1.3; c)any differences in outcomes according to: line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA (r-axSpA/nr-axSpA). Methods Consecutive patients with active axSpA (diagnosis according Assessment of SpondyloArthritis International Society ASAS criteria), who started SEC treatment, were evaluated prospectively. Data on disease characteristics, previous/ongoing treatments and imaging were collected. Disease-activity/functional/clinical scores and biochemical values were recorded at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and LDA at T6. Infections, adverse events were recorded. Results 249 patients (47.8% male; median age 51 years) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0=3.5(2.9-4.4) vs. T24=1.9(1.2-2.4);p=0.02] and BASDAI [T0=6.5(5.0-7.5) vs. T24=2.8(1.8-4.0);p=0.03]. After 24-months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI&lt;4). At T24 naïve-patients showed better physical-functioning and lower disease-activity than non-naïve (Table 1). Similarly, at T24 we observed better physical functioning and lower inflammatory activity in males vs. females and in nr-axSpA vs. r-axSpA subjects. Retention-rate at T24 was 75% in the whole population, with some difference depending on gender (log-rank 9.319; p=0.002) (Figure 1). Treatment was discontinued in 61 patients (24.5%), mainly due to primary/secondary loss of effectiveness events (20 and 24 subjects, respectively), and only 17 patients (6.8%) due to adverse events (7 for reactions at the injection site or skin manifestations, 1 for gastro-intestinal complications, 1 for relapsing uveitis, 1 for hypertransaminasemia, 4 for severe recurrent infections, 3 due to the onset of new cancer). Table 1. Clinical, functional, disease activity and serological parameters of naïve (n=72) and non-naïve (n=177) axSpA patients during the 24-month follow-up T0 T6 T12 T24 BASMI [0-10], median (IQR ) naïve 2.0 (1.0-4.0) 2.0 (0.0-3.3) 1.0 (0.0-2.8) 1.0 (0.0-2.0) non-naïve 4.0 (1.0-7.0) 4.0 (1.0-7.0) 2.0 (1.0-4.0) 2.0 (1.0-3.0) p p=0.03 p=0.04 ns ns HAQ-S [0-8], median (IQR ) naïve 0.8 (0.5-1.3) 0.5 (0.0-1.0) 0.3 (0.0-1.0) 0.1 (0.0-0.5) non-naïve 1.1 (0.8-1.5) 1.0 (0.4-1.3) 0.6 (0.4-0.9) 0.7 (0.1-0.9) p p=0.04 p=0.04 p=0.04 p=0.04 ASDAS [0-6], median (IQR ) naïve 3.3 (2.7-3.9) 2.1 (1.6-2.7) 2.0 (1.2-2.8) 1.3 (1.0-2.2) non-naïve 3.7 (2.9-4.7) 2.9 (2.0-3.7) 2.1 (1.9-3.1) 2.3 (1.6-2.3) p ns ns ns p=0.04 ESR [0-25](mm/h), median (IQR ) naïve 14.0 (6.0-27.0) 10.0 (4.0-19.5) 8.0 (3.1-12.8) 5.0 (2.0-15.0) non-naïve 18.5 (10.0-31.3) 15.0 (8.0-25.0) 12.0 (6.0-20.0) 12.0 (6.0-19.0) p p=0.04 p=0.04 p=0.04 p=0.04 Legend: BASMI: Bath Ankylosing Spondylitis Metrology Index; HAQ: Health Assessment Questionnaire modified for spondyloarthritis; ASDAS: Ankylosing Spondylitis Disease Activity Score; ESR: erythrocyte sedimentation rate Conclusion In a real-life clinical-setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug-retention-rate. No differences were observed between r-axSpA and nr-axSpA. Acknowledgements Contributing authors of the Spondyloartritis and Psoriatic Arthritis SIR Study Group “Antonio Spadaro”: Alberto Cauli, MD, PhD, Rheumatology Unit, Department of Medical Sciences, AOU and University of Cagliari, Cagliari, Sardegna, Italy; Angelo Semeraro, MD, Rheumatology Unit, Martina Franca-ASL Taranto, Puglia, Italy; Leonardo Santo, MD, Rheumatology Unit, ASL BT Andria – DSS4 Barletta, Italy, Barletta-Andria-Trani, Puglia, Italy; Emanuela Praino, MD, Rheumatology Unit, ASL BT Andria – DSS4 Barletta, Italy, Barletta-Andria-Trani, Puglia, Italy; Giorgio Amato, MD, Rheumatology Unit, A.O.U. Policlinico S. Marco, Catania, Sicilia, Italy; Nicolò Girolimetto, MD, Rheumatology Unit, Department of Internal Medicine, Azienda USL-IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Emilia Romagna, Italy. Disclosure of Interests Giacomo Cozzi: None declared, Mariagrazia Lorenzin: None declared, Maria Sole Chimenti: None declared, Salvatore D’Angelo: None declared, Antonio Marchesoni: None declared, Carlo Salvarani: None declared, Ennio Lubrano: None declared, Luisa Costa: None declared, Ylenia Dal Bosco: None declared, Elena Fracassi: None declared, Augusta Ortolan: None declared, Mario Ferraioli: None declared, Antonio Carriero: None declared, elisa visalli: None declared, RICCARDO BIXIO: None declared, Francesca Desiati: None declared, ALBERTO BERGAMINI: None declared, elisa pedrollo: None declared, Andrea Doria Grant/research support from: Novartis, Abbvie, Pfizer, MSD, Janssen, Rosario Foti: None declared, Antonio Carletto: None declared, Roberta Ramonda Grant/research support from: Novartis, Abbvie, Pfizer, MSD, Janssen